P. Polosa

Effects of Cholecystokinin Octapeptide on the Hypothalamic-Pituitary-Adrenal Axis Function and on Vasopressin, Prolactin and Growth Hormone Release in Humans

Cholecystokinin (CCK), a gastrointestinal (GI) hormone, is also present in structures of the central nervous system such as cortex, hippocampus, amygdala, olfactory tubercle and in regions involved in the regulation of the pituitary function. Although a number of studies have evaluated the effects of CCK on hypothalamic-pituitary-adrenal (HPA) axis function and on arginine vasopressin (AVP), prolactin (PRL) and growth hormone (GH) plasma levels in the laboratory animal, its role in humans has not been explored. Hence, we examined the effects of the exogenous administration of this GI hormone on corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), cortisol, AVP, PRL and GH plasma levels in humans. To accomplish this, graded doses (0, 50, 140 and 420 ng/kg) of sulfated CCK octapeptide (CCK-8), the full biologically active peptide, were infused intravenously to healthy men in 30 min. Blood samples were collected 30 min and immediately before the infusion was started (baseline) and 15, 30, 45, 60 and 90 min thereafter. CRH, ACTH, and AVP were extracted from plasma proteins using cartridges of SepPak C18. These hormones and cortisol were measured by radioimmunoassay whereas PRL and GH were measured by immunoradiometric assay. CCK-8 increased plasma ACTH and cortisol levels only at the dose of 420 ng/kg, whereas it had no detectable effect on plasma CRH levels. It increased also plasma AVP levels at the doses of 140 and 420 ng/kg. However, this effect reached the statistical significance only at the highest dose tested. CCK-8 stimulated PRL and GH release in a dose-dependent fashion. The lowest stimulatory dose was 140 ng/kg for both hormones.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of dexamethasone on thyroid hormone response to TSH

The effect of short-term dexamethasone administration (8 mg daily for 3 days) on thyroid hormone response to exogenous TSH (bovine TSH, 5 IU i.m.) was studied in 16 euthyroid volunteers. Serum T3 and T4 concentrations were measured by radio-immunoassay prior to and 2, 6, 12, 24, and 49 hr after bTSH injection, both under basal conditions and during dexamethasone treatment. In all subjects bTSH administration raised both T3 and T4 concentrations significantly. Dexamethasone treatment induced a slight depression of endogenous TSH (m +/- SEM = 2.0 +/- 0.4 versus 1.6 +/- 0.3 muU/ml) and T4 (6.8 +/- 0.4 versus 6.1 +/- 0.2 mug/100 ml) basal values and a significant decrease in T3 value (1.16 +/- 0.09 versus 0.64 +/- 0.06 ng/ml, p = 0.005). The mean increment of both T3 and T4 after bTSH injection was percentually unchanged during dexamethasone treatment but, due to lowered basal value, T3 levels at each time interval after TSH + dexamethasone were significantly lower than the corresponding values observed after TSH alone. The present data show that high dexamethasone doses decrease T3 serum levels significantly without inhibiting T3 response to TSH stimulation. Only a slight lowering was observed in T4 levels.

ROLE OF PERIPHERALLY INFUSED ANGIOTENSIN II ON THE HUMAN HYPOTHALAMIC-PITUITARY-ADRENAL AXIS

Although angiotensin II (All), a potent vasoconstrictor agent, has been reported to stimulate the hypothalamicpituitary‐adrenal (HPA) axis of laboratory animals, Its role In the regulation of this axis In humans appears to be controversial. To examine this question, All (Val5‐All amide) was Infused Intravenously Into 19 male normal volunteers at the doses of 0, 1, 3·3 and 10 ng/kg/mln for 30 min. All had no effect on plasma ACTH, cortical, corticotrophin‐releasing hormone, arginine vasopressin, and atrial natriuretic factor concentrations, nor did it increase systolic or diastolic arterial blood pressure. On the other hand, All caused a dose‐dependent Increase of plasma aldosterone concentrations, suggesting that the doses and the mode of All Infusion were effective. Thus, our data show that peripherally Infused All has no detectable effect on the HPA axis function in humans, at doses capable of stimulating plasma aldosterone secretion, Its specific target hormone

FURTHER STUDIES ON THE EFFECTS OF DIHYDROTESTOSTERONE ON GONADOTROPHIN RELEASE INDUCED BY LH-RH IN MEN

In order to determine the effect of dihydrotestosterone on the feed‐back mechanism of the hypothalamo‐pituitary testis axis, seven men were subjected to LH‐RH tests before and after treatment with dihydrotestosterone.

EFFECT OF OESTRADIOL ON GONADOTROPHIN RELEASE INDUCED BY LHRH IN MEN

In order to study the role of the oestradiol on the feed‐back mechanism, fourteen men were subjected to LHRH test before and after treatment with oestradiol. The oestrogen was administered i.m., 3 μg/kg/24 h and 150 μg/kg/24 h, in two groups of patients. Doses of 3 and 150 μg respectively produced a reduction of LH release of 74% and 60% below control. FSH response to LHRH was almost abolished by oestrogens. Our findings show that oestrogensin men decrease the pituitary response to LHRH.

Thyrotropin and Prolactin Response to Intraspinal TRH Administration in Man

The effect of intraspinal (i.s.) TRH administration of Prolactin (Prl) and thyrotropin stimulating hormone (TSH) serum levels was studied in order to verify the existence of a ventricular route in man for releasing factor delivery to the anterior pituitary, which has been previously reported in rats. Ten young male subjects were given 200 microgram thyrotropin releasing hormone (TRH) i.s. injections and Prl and TSH were measured by radioimmunoassay (RIA) before and at various times after TRH administration. In the same subjects, an i.v. TRH test was also performed. After i.s. TRH, a prompt Prl increase (peak values at 10-30 min and return to baseline within 150 min) and a delayed increase (3-5 h following TRH injection) were observed in 7 and 5 subjects respectively, while an early elevation in serum TSH occurred in 6 subjects and a late one in other 6. In two subjects, a biphasic response of both tropins was present. Prl and TSH response to i.v. TRH was within the normal range in all cases; no late rise of the 2 hormones was observed. A kinetic experiment with 125I-TRH was also carried out to elucidate the mode of i.s. vs i.v. TRH action. These results confirm in man data reported in animals which suggest that TRH can be transported from the cerebrospinal fluid (CSF) to the portal system and the hypophysis.

Triiodothyronine and Thyrotropin-Releasing Hormone Interaction on TSH Release in Man

In order to study thyrotropin releasing hormone (TRH)-thyroid hormone interaction, we examined thyrotropin (TSH) behaviour after synthetic TRH administration in 24 euthyroid subjects, 3 patients with

Limited clinical usefulness of plasma corticotropin-releasing hormone, adrenocorticotropin and ß-endorphin measurements as markers of lung cancer.

We measured plasma corticotropin-releasing hormone (CRH), ACTH, ß-endorphin (ß-EP), and Cortisol levels as possible tumor markers in a sequence of 103, randomly selected, patients with lung cancer but without the ectopic Cushing’s syndrome and in 72 age-and sex-matched controls. Plasma CRH levels of cancer patients were similar to those of controls both in patients sampled in the morning or in the afternoon. On the other hand, plasma ACTH levels of cancer patients were significantly higher than control patients both in the morning and in the afternoon and showed a preserved circa-dian rhythm. However, about 35% of cancer patients sampled in the morning and about 60% of those sampled in the afternoon had ACTH levels within the 95% confidence interval (CI) of controls. Also plasma ß-EP levels were more elevated in cancer patients than controls in the morning but about 33% of them and about 80% of those sampled in the afternoon had ß-EP levels within the 95% CI of controls. Despite the higher plasma ACTH levels, cancer patients had Cortisol plasma levels similar to controls with preserved circadian rhythm. In conclusion, although mean plasma ACTH and ß-EP were higher in patients affected by lung cancer, their measurements, as well as those of CRH, have practically no diagnostic value. Perhaps measurement of ACTH levels in the bronchial lavage may be more helpful.

HYDROTESTOLACTONE LOWERS SERUM OESTRADIOL AND PRL LEVELS IN NORMAL MEN: EVIDENCE OF A ROLE OF OESTRADIOL IN PRL SECRETION*

The effect on serum PRL levels of lowering serum oestradiol (E2) concentration by short‐term administration of an aromatase activity inhibitor, hydrotestolactone (HT), was studied in six healthy male subjects. After HT administration serum E2 levels decreased from 68 ± 5±8 to 26 ± 2±5 pmol/1 (mean ± SE, P < 0±05). These E2 changes were accompanied by a significant decrease in mean 2‐h PRL levels from 11±2 ± 2±1 to 6±5 ± 1±6 ng/ml mean ± SE, P < 0±05). The evaluation of individual percentage change from basal concentrations showed a varying decrease in all subjects. These findings suggest that under physiological conditions E2 may be one of the factors which control blood PRL concentrations in men.

High incidence of anti-GH antibodies in subjects treated with the GH clinical preparation available in Italy

We have characterized the GH clinical preparation available in Italy (Grorm, Serono) by gel chromatography and immunoreactivity. Only 50–60% of this preparation can be identified with the active GH monomeric form. Both higher and lower molecular weight compounds are present as well. Then, using a radioimmunoassay technique, we looked for anti-GH antibodies in 21 subjects under Grorm treatment and found them in 6 patients (28.6%). Two subjects having anti-GH antibodies with high affinity had a lower growth rate. These data suggest that anti-GH antibodies measurement is clinically useful in patients treated with this GH preparation. A more purified preparation should be used when a slowing down of the growth rate is observed in the presence of anti-GH antibodies.